The aims of this proposal are to determine the role of complement activation, which occurs during cardiopulmonary bypass, on heart and lung function after bypass. The PI has utilized a neonatal piglet model with cardiopulmonary bypass and hypothermia to demonstrate that there is significant activation of various complement pathways resulting in direct injury to myocardium and lungs. They will first determine the effects of blocking the various pathways of complement activation on recovery of heart and lung function after bypass, and in the second part of these studies they will perform similar mechanistic analysis using a neonatal cardiac myocyte model. In subsequent studies they will determine the role of complement activation on cardiac myofilament structure and function and the effects of activation of proteolytic activity on the contractile proteins. In the final phase they will utilize a reconstitution strategy to replace defective troponin proteins to determine if they can restore cardiac function by this approach. Ultimately, the goal would be to induce expression of these proteins to improve cardiac recovery.